The present invention relates to novel unsymmetrical chiral diphosphines and phosphine phosphinites and their synthesis and to complexes of these compounds with metals of groups VIIb, VIIIb and Ib of the Periodic Table and also to their use as catalysts for enantioselective transformations, in particular hydrogenations.
Trisubstituted organophosphorus compounds are of great importance as ligands in homogeneous catalysis. Variation of the substituents of phosphorus in such compounds enables the electronic and steric properties of the phosphorus ligands to be influenced in a tailored manner, so that selectivity and activity in homogeneously catalyzed processes can be controlled.
Enantiomerically enriched chiral ligands are used in asymmetric synthesis or asymmetric catalysis, where the important aspect is that the electronic and stereochemical properties of the ligand are optimally matched to the respective catalysis problem. There is therefore a great need for chiral ligands which are stereochemically and electronically different in order to find the optimum xe2x80x9ctailoredxe2x80x9d ligand for a particular asymmetric catalysis.
The structural variety of phosphorus ligands known hitherto is very wide. These ligands can be classified, for example, according to class of substance and examples of such classes of substances are trialkylphosphines and triarylphosphines, phosphites, phosphinites, phosphonites, aminophosphines, etc. This classification according to class of substance is particularly useful for describing the electronic properties of the ligands.
Phosphorus ligands can also be classified according to their symmetry properties or according to the denticity of the ligands. This structuring takes account, in particular, of the stability, activity and stereoselectivity of metal complexes with phosphorus ligands as catalyst precursors or as catalysts. Apart from the widespread C2-symmetrical bidentate ligand systems such as DUPHOS, DIPAMP, BINAP or DEGUPHOS, unsymmetrical bidentate organophosphorus ligands are increasingly becoming the focus of asymmetric catalysis. Important examples are the large class of versatile chiral ferrocenylphosphine ligands such as JOSIPHOS, DPPM, the bisphosphinite ligands such as CARBOPHOS which are used particularly successfully in the asymmetric hydrogenation of olefins and imines, or the phosphine phosphite ligands such as BINAPHOS or BIPHEMPHOS which are used successfully in the asymmetric hydroformylation of olefins. 
An important aspect of the success of these classes of compound is believed to be the creation of a particularly asymmetric environment around the metal center by these ligand systems. To utilize such an environment for an effective transfer of chirality, it is advantageous to control the flexibility of the ligand system as inherent limitation of the asymmetric induction.
Disadvantages of the chiral phosphorus ligand systems known hitherto are, firstly, their complicated synthesis and, secondly, the restricted opportunities for varying the properties of a given ligand skeleton, e.g. by the introduction of different substituents.
It is an object of the present invention to provide novel, unsymmetrical, bidentate and chiral phosphorus ligand systems which can easily be varied in terms of their steric and electronic properties over an extraordinarily wide range.
This object is achieved by a class of chiral, unsymmetrical bidentate organophosphorus compounds of the formula (I) in which a chiral bicycloaliphatic skeleton is present.
The present invention accordingly provides compounds of the formula (I), 
where
m and n may each be, independently of one another, 0 or 1 and
R1-R2 are, independently of one another, a radical selected from the group consisting of C1-C24-alkyl, C3-C8-cycloalkyl which may contain 1-2 heteroatoms selected from the group consisting of N, O and S, C6-C14-aryl, phenyl, naphthyl, fluorenyl and C2-C13-heteroaryl in which the number of heteroatoms selected from the group consisting of N, O and S may be 1-4.
The cyclic aliphatic or aromatic radicals are preferably 5- and 6-membered rings.
The abovementioned radicals may themselves each be monosubstituted or polysubstituted. These substituents may be, independently of one another, hydrogen, C1-C20-alkyl, C2-C20-alkenyl, C1-C10-haloalkyl, C3-C8-cycloalkyl, C2-C9-heterocycloalkyl, C6-C10-aryl, phenyl, naphthyl, fluorenyl, C2-C6-heteroaryl in which the number of heteroatoms, in particular from the group consisting of N, O and S, may be 1-4, C1-C10-alkoxy, preferably OMe, C1-C9-trihalomethylalkyl, preferably trifluoromethyl and trichloromethyl, halo, in particular fluoro and chloro, nitro, hydroxy, trifluoromethylsulfonato, oxo, amino, C1-C8-substituted amino of the formulae NH-alkyl-C1-C8, NH-aryl-C5-C6, N-alkyl2-C1-C8, N-aryl2-C5-C6, N-alkyl3-C1-C8+, N-aryl3-C5-C6+, NHxe2x80x94CO-alkyl-C1-C8, NHxe2x80x94CO-aryl-C5-C6, cyano, carboxylato of the formulae COOH and COOQ, where Q is either a monovalent cation or C1-C8-alkyl, C1-C6-acyloxy, sulfinato, sulfonato of the formulae SO3H and SO3Q, where Q is either a monovalent cation, C1-C8-alkyl or C6-aryl, phosphato of the formulae PO3H2, PO3HQ and PO3Q2, where Q is either a monovalent cation, C1-C8-alkyl or C6-aryl, tri-C1-C6-alkylsilyl, in particular SiMe3, and/or where two radicals R1 or two radicals R2 may be connected to one another, preferably forming a 4-8-membered ring which may be substituted by linear or branched C1-C10-alkyl, C6-aryl, benzyl, C1-C10-alkoxy, hydroxy or benzyloxy.
R3-R10 are each, independently of one another, a hydrogen atom or a radical selected from the group consisting of C1-C24-alkyl, C1-C10 -haloalkyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl which may also contain 1-2 heteroatoms selected from the group consisting of N, O and S, C6-C14-aryl, phenyl, naphthyl, fluorenyl and C2-C13-heteroaryl in which the number of heteroatoms selected from the group consisting of N, O and S may be 1-4.
The cyclic aliphatic or aromatic radicals here are preferably 5- to 7-membered rings.
The abovementioned groups may themselves each be monosubstituted or polysubstituted. The substituents may be selected independently from the group consisting of hydrogen, C1-C20-alkyl, C2-C20-alkenyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl, C2-C9-heteroalkyl, C1-C9-heteroalkenyl, C6-C10-aryl, C,1-C10-haloalkyl, phenyl, naphthyl, fluorenyl, C2-C6-heteroaryl in which the number of heteroatoms, in particular from the group consisting of N, O and S, may be 1-4,
C1-C10-alkoxy, trichloromethyl, fluoro, oxo, amino, C1-C8-substituted amino of the formulae N-alkyl2-C1-C8, N-aryl2-C5-C6, N-alkyl3-C1-C8+, N-aryl3-C5-C6+,
and where R5 and R6 may be connected so as to form a 5-7-membered cyclic aromatic or aliphatic compound.
P is trivalent phosphorus.
The invention also provides complexes comprising a chiral bidentate organophosphorus ligand of the formula (I) with at least one metal. Such complexes are obtainable by simple mixing of the organophosphorus compounds of the invention with metal complex precursors in solution.
It is preferred that
R1-R2,are each, independently of one another, a radical selected from the group consisting of C1-C6-alkyl, C5-C6-cycloalkyl, C6-aryl, phenyl, naphthyl, C4-C5-heteroaryl in which the number of heteroatoms selected from the group consisting of N, O and S is 1, where the abovementioned aromatic or heteroaromatic groups may themselves each be monosubstituted to trisubstituted. The substituents may be selected independently from the group consisting of hydrogen, C1-C6-alkyl, C2-C4-alkenyl, C1-C6-haloalkyl, C2-C6-heteroalkyl, C6-aryl, phenyl, naphthyl, fluorenyl, C3-C5-heteroaryl, in which the number of heteroatoms selected from the group consisting of N, O and S may be 1-2, C1-C6-alkoxy, preferably OMe, C1-C9-trihalomethylalkyl, preferably trifluoromethyl and trichloromethyl, halo, in particular fluoro and chloro, nitro, hydroxy, trifluoromethylsulfonato, oxo, amino, C1-C6-substituted amino of the formulae NH2, NH-alkyl-C1-C6, NH-aryl-C6, N-alkyl2-C1-C6, N-aryl2-C6, N-alkyl3-C1-C6+, N-aryl3-C6+, NHxe2x80x94CO-alkyl-C1-C6, NHxe2x80x94CO-aryl-C6, in particular NMe2, NEt2, cyano, carboxylato of the formulae COOH and COOQ, where Q is either a monovalent cation or C1-C4-alkyl, C1-C6-acyloxy, sulfinato, sulfonato of the formulae SO3H and SO3Q, where Q is either a monovalent cation, C1-C4-alkyl or C6-aryl, phosphato of the formulae PO3H2, PO3HQ and PO3Q2, where Q is either a monovalent cation, C1-C4-alkyl or C6-aryl, tri-C1-C6-alkylsilyl, in particular SiMe3.
R1-R10 in the ligand system of the invention preferably contain, independently of one another, alkyl, alkenyl, cycloalkyl, alkoxy, trialkylsilyl or/and dialkylamino groups which each contain from 1 to 20, in particular from 1 to 6, carbon atoms.
Among the group of alkyl substituents, preference is given to methyl, ethyl, n-propyl, 1-methylethyl, n-butyl, 1-methylpropyl, 1,1-dimethylethyl, n-pentyl, 1-methylbutyl, 2-methylethyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, n-hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl, n-heptyl, n-octyl, n-nonyl, n-decyl.
Among cyclic alkyl substituents, particular preference is given to substituted and unsubstituted cyclopentyl, cyclohexyl and cycloheptyl radicals.
Preferred alkenyl substituents are vinyl, propenyl, isopropenyl, 1-butenyl, 2-butenyl, 1-pentenyl, 2-pentenyl, 2-methyl-1-butenyl, 2-methyl-2-butenyl, 3-methyl-1-butenyl, 1-hexenyl, 1-heptenyl, 2-heptenyl, 1-octenyl or 2-octenyl. Among cyclic alkenyl substituents, particular preference is given to cyclopentenyl, cyclohexenyl, cycloheptenyl and norbornyl.
As aryl substituents in R1-R2, particular preference is given to 2-alkylphenyl, 3-alkylphenyl, 4-alkylphenyl, 2,6-dialkylphenyl, 3,5-dialkylphenyl, 3,4,5-trialkylphenyl, 2-alkoxyphenyl, 3-alkoxyphenyl, 4-alkoxyphenyl, 2,6-dialkoxyphenyl, 3,5-dialkoxyphenyl, 3,4,5-trialkoxyphenyl, 3,5-dialkyl-4-alkoxyphenyl, 3,5-dialkyl-4-dialkylaminophenyl, 4-dialkylamino, where the abovementioned alkyl and alkoxy groups preferably each contain from 1 to 6 carbon atoms, 3,5-trifluoromethyl, 4-trifluoromethyl, 2-sulfonyl, 3-sulfonyl, 4-sulfonyl, monohalogenated to tetrahalogenated phenyl and naphthyl.
Preferred halogen substituents are F, Cl and Br.
All haloalkyl or/and haloaryl groups preferably have the formulae CHal3, CH2CHal3, C2Hal5, where Hal may be, in particular F, Cl or Br. Particular preference is given to haloalkyl or/and haloaryl groups of the formulae CF3, CH2CF3, C2F5.
Finally, preference is given to optically active ligand systems of the formula (I) which are enriched in one enantiomer. Particular preference is given to ligand systems in which the enantiomeric enrichment exceeds 90%, in particular 99%.
The class of bidentate organophosphorus compounds provided by the invention has a chiral ligand skeleton which is simple to modify in a variety of ways and can be varied within a very wide range in respect of its steric and electronic properties by the simple introduction of widely differing substituents. In metal complexes, organophosphorus compounds of the formula (I) are able to create a highly asymmetric coordination sphere with independently modifiable organophosphorus donors on the metal center and thus make effective asymmetric induction possible. In addition, the flexibility of the coordination sphere of the complex can be controlled in steric terms via the easy introduction of a wide variety of substituents into the organophosphorus ligands.
Thus, a wide range of applications is possible for the compounds of the formula (I) since the bidentate phosphorus ligands can be optimized sterically and electronically according to the catalytic synthesis by the introduction of suitable substituents.
At the same time, the compounds of the invention can, in contrast to many established ligand systems, be synthesized particularly simply in a wide range of variations from simple starting materials. This makes it possible for the ligands of the present invention to be prepared industrially without problems.
Various methods using readily obtainable starting materials are available for the synthesis of compounds of the formula (I).
Phosphorus compounds according to the invention from the class of phosphines phosphinites can be prepared, for example, as follows:
Starting from a 10-camphorsulfonic acid derivative, the salt of the camphorsulfonic acid derivative can firstly be prepared in an aqueous basic medium and the sulfonic acid radical can then be replaced by a halide radical in the presence of a phosphorus trihalide. In an alternative method, the replacement of the sulfonic acid radical by a halide radical is carried out in a single-step synthesis in the presence of molecular halogen and PR3. Preferred phosphorus trihalides are PBr3 and PI3, preferred molecular halogens are Br2 and I2. Subsequent reduction gives the corresponding isoborneol derivative. In further process steps, the hydroxy group of the camphor derivative is silylated and subsequently phosphinated in the 10 position with replacement of the halogen by means of an alkali metal salt of a phosphine AP(R1)2. The phosphine group is protected by addition of a borane adduct. Removal of the protective group from the hydroxy group is carried out by customary methods, e.g. by addition of tetrabutylammonium fluoride (TBAF). The hydroxy group is then phosphinated in a basic medium by addition of a phosphine halide HalP(R2)2. The newly introduced second phosphorus-containing group can likewise be protected by addition of a borane adduct. The removal of the protective borane groups is carried out using a nitrogen base. The phosphine phosphinites of the invention are obtained.
The diphosphines can be prepared from the corresponding phosphine phosphinites by rearrangement of the phosphinite group to the phosphine oxide by heating and subsequent reduction to the diphosphine.
The choice of an appropriate preparative method depends on the availability of the corresponding starting materials and on the desired substitution pattern.
The abovementioned processes will be described in more detail below with the aid of general preferred process examples.
Monosubstituted bicyclic skeletons are available from the chiral pool. 10-bromocamphor is prepared in a three-stage process, as described above, based on literature methods ((a) F. Dallacker, I. Alroggen, H. Krings, B. Laurs, M. Lipp, Liebigs Ann. Chem. 1961, 647, 23-36; (b) F. Dallacker, K. Ulrichs, M. Lipp, Liebigs Ann. Chem. 1963, 667, 50-55; (c) N. Proth, Rev. Tech. Lux 1976, 4, 195-199). 
A more advantageous synthetic method is a single-stage synthesis of 10-iodocamphor from 10-camphorsulfonic acid (S. Oae, H. Togo, Bull. Chem. Soc. Jpn. 1983, 56, 3802-3812), followed by a selective reduction of the carbonyl group using lithium aluminum hydride to give the iodoalcohol. 
The free hydroxy group is protected by a protective silyl group by addition of Et3SiCl in the presence of a base, and the side chain is subsequently phosphinated using lithium salts of dialkylphosphines or diarylphosphines. All of the abovementioned radicals R1 can be introduced selectively by choice of an alkali metal salt of an appropriate phosphine. The phosphine is converted into the borane complex by means of a borane THF adduct and desilylation using TBAF gives the hydroxyphosphine in high yields. 
The introduction of the second phosphine unit is achieved by deprotonation of the hydroxy group and reaction with a chlorophosphine to selectively introduce the group P(OnR2)2. The phosphine phosphinite can likewise be converted into the borane complex by means of a borane-THF adduct. Decomplexation is carried out by addition of a nitrogen base. 
To prepare the diphosphines, the phosphine phosphinites are rearranged thermally in solution at a temperature of from 100xc2x0 C. to 200xc2x0 C. with the inversion of the stereochemistry to give the phosphine oxide. Subsequent reduction gives the diphosphine. 
The compounds of the formula (I) can be used as ligands on metals in asymmetric, metal-catalyzed reactions (e.g. hydrogenation, hydroformylation, rearrangement, allylic alkylation, cyclopropanation, hydrosilylation, hydride transfers, hydroborations, hydrocyanations, hydrocarboxylations, aldol reactions or the Heck reaction) and also in polymerizations. They are particularly useful for asymmetric reactions.
Suitable complexes, in particular those of the formula (II), contain novel compounds of the formula (I) as ligands.
[MxPyLzSq]Arxe2x80x83xe2x80x83(II)
In the formula (II), M is a transition metal center, L are identical or different coordinating organic or inorganic ligands and P are novel bidentate organophosphorus 20 ligands of the formula (I), S are coordinating solvent molecules and A are equivalents of noncoordinating anions, where x is 1 or 2, y is an integer greater than or equal to 1 and z, q and r are, independently of one another, integers greater than or equal to 0.
The upper limit on the sum y+z+q is imposed by the number of coordination centers available on the metal centers, with not all coordination sites having to be occupied. Preference is given to complexes having an octahedral, pseudooctahedral, tetrahedral, pseudotetrahedral or square planar coordination sphere, which may also be distorted, around the respective transition metal center. In such complexes, the sum y+z+q is smaller than or equal to 6x.
The complexes of the invention contain at least one metal atom or ion, preferably a transition metal atom or ion, in particular selected from the group consisting of palladium, platinum, rhodium, ruthenium, osmium, iridium, cobalt, nickel or/and copper.
Preference is given to complexes having less than four metal centers, particularly preferably those having one or two metal centers. The metal centers can be occupied by different metal atoms and/or ions.
Preferred ligands L in such complexes are halide, in particular Cl, Br and I, diene, in particular cyclooctadiene, norbornadiene, olefin, in particular ethylene and cyclooctene, acetato, trifluoroacetato, acetylacetonato, allyl, methallyl, alkyl, in particular methyl and ethyl, nitrile, in particular acetonitrile and benzonitrile, and also carbonyl and hydrido ligands.
Preferred coordination solvents S are amines, in particular triethylamine, alcohols, in particular methanol, and aromatics, in particular benzene and cumene.
Preferred noncoordinating anions A are trifluoroacetate, trifluoromethanesulfonate, BF4, CIO4, PF6, SbF6 and BAr4.
In the individual complexes, the different molecules, atoms or ions of the individual constituents M, P, L, S and A may be present.
Among complexes having an ionic structure, preference is given to compounds of the type [RhP(diene)]+Axe2x88x92, where P is a novel ligand of the formula (I).
These metal-ligand complexes can be prepared in situ by reaction of a metal salt or a corresponding precursor complex with the ligands of the formula (I). It is also possible to obtain a metal-ligand complex by reaction of a metal salt or a corresponding precursor complex with the ligands of the formula (I) and subsequent isolation. Such a complex is preferably produced in a single-vessel reaction while stirring at elevated temperature. Catalytically active complexes can also be produced directly in the reaction mixture of the planned catalytic reaction.
Examples of metal salts are metal chlorides, bromides, iodides, cyanides, nitrates, acetates, acetylacetonates, hexafluoroacetylacetonates, tetrafluoroborates, perfluoroacetates or triflates, in particular of palladium, platinum, rhodium, ruthenium, osmium, iridium, cobalt, nickel or/and copper. Examples of precursor complexes are: cyclooctadienepalladium chloride, cyclooctadienepalladium iodide, 1,5-hexadienepalladium chloride, 1,5-hexadienepalladium iodide,bis(dibenzylideneacetone)palladium, bis(acetonitrile)palladium(II) chloride, bis(acetonitrile)palladium(II) bromide, bis(benzonitrile)palladium(II) chloride, bis(benzonitrile)palladium(II) bromide, bis(benzonitrile)palladium(II) iodide,bis(allyl)palladium, bis(methallyl)palladium, allylpalladium chloride dimer, methallylpalladium chloride dimer, tetramethylethylenediaminepalladium dichloride, tetramethylethylenediaminepalladium dibromide, tetramethylethylenediaminepalladium diiodide,(tetramethylethylenediamine)dimethylpalladium, cyclooctadieneplatinum chloride, cyclooctadieneplatinum iodide, 1,5-hexadieneplatinum chloride, 1,5-hexadieneplatinum iodide, bis(cyclooctadiene)platinum, potassium ethylenetrichloroplatinate, cyclooctadienerhodium(I) chloride dimer, norbornadienerhodium(I) chloride dimer, 1,5-hexadienerhodium(I) chloride dimer, tris(triphenylphosphine)rhodium(I) chloride, hydridocarbonyltris(triphenylphosphine)rhodium(I) chloride, bis(cyclooctadiene)rhodium(I) perchlorate, bis(cyclooctadiene)rhodium(I) tetrafluoroborate, bis(cyclooctadiene)rhodium(I) triflate, bis(acetonitrile)cyclooctadienerhodium(I) perchlorate, bis(acetonitrile)cyclooctadienerhodium(I) tetrafluoroborate, bis(acetonitrile)cyclooctadienerhodium(I) triflate, cyclopentadienylrhodium(III) chloride dimer, pentamethylcyclopentadienylrhodium(III) chloride dimer, (cyclooctadiene)Ru(xcex73-allyl)2, ((cyclooctadiene)Ru)2 (acetate)4, ((cyclooctadiene)Ru)2 (trifluoroacetate)4, RuCl2 (arene) dimer, tris(triphenylphosphine)ruthenium(II) chloride, cyclooctadieneruthenium(II) chloride, OsCl2(arene) dimer, cyclooctadieneiridium(I) chloride dimer, bis(cyclooctene)iridium(I) chloride dimer,bis(cyclooctadiene)nickel, (cyclododecatriene)nickel, tris(norbornene)nickel, nickel tetracarbonyl, nickel(II) acetylacetonate, (arene)copper triflate, (arene)copper perchlorate, (arene)copper trifluoroacetate, cobalt carbonyl.
The complexes based on one or more metals, in particular metals selected from the group consisting of Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu, may themselves be catalysts or can be used for preparing catalysts based on one or more metals, in particular metals selected from the group consisting of Ru, Co, Rh, Ir, Ni, Pd, Pt, Cu. All these complexes are particularly suitable for the asymmetric hydrogenation of Cxe2x95x90C, Cxe2x95x90O or Cxe2x95x90N bonds in which they display high activities and selectivities and for asymmetric hydroformylation. In particular, it is advantageous that the ligands of the formula (I) can be very readily matched to the respective substrate and the catalytic reaction in steric and electronic terms due to the wide variety of modifications which are readily possible.
Corresponding catalysts comprise at least one of the complexes of the invention.
In view of the teachings herein one of ordinary skill in the art can prepare the invention complexes and catalysts.
German application 100 52 868.6, filed on Oct. 25, 2000, is incorporated herein by reference in its entirety.